CT灌注成像在定量监测肿瘤微血管系对抗血管生成治疗反应中的应用

CT perfusion imaging in quantitative monitoring for tumour microvascular responses to anti-angiogenesis therapy in rabbits

目的探讨CT灌注成像技术对定量评价肿瘤组织血流动力学改变,区分肿瘤组织和正常组织、肿瘤中心组织和肿瘤边缘组织的有效性,以及定量监测肿瘤微血管系对抗血管生成药物治疗反应的有效性。方法 15只一侧大腿植入VX2肿瘤的新西兰大白兔分为2组,1组行抗血管治疗(n=11),1组为对照组(n=4)。于肿瘤种植1周后、治疗1周后和治疗2周后进行DEC-CT扫描,分别计算肿瘤区、肿瘤边缘区、肿瘤中心区和正常组织区的灌注参数:血流量(blood flow,BF)、血容量(blood volume,BV)、平均通过时间(meantransit time,MTT)和表面通透性(permeability surface,PS),并对各灌注参数值进行统计分析。结果肿瘤区和正常组织区的BF、PS、MTT值分别为(149.32±30.99)ml/(100g.min)、(28.24±5.15)ml/(100g.min)、(2.79±0.66)s和(32.18±4.10)ml/(100g.min)、(11.88±0.71)ml/(100g.min)、(6.57±0.90)s,两者比较差异均有统计学意义(P<0.01)。肿瘤核心区和肿瘤边缘区的BF、PS、MTT值分别为(175.70±34.43)ml/(100g.min)、(32.43±6.52)ml/(100g.min)、(3.87±0.84)s和(19.07±3.58)ml/(100g.min)、(18.75±2.10)ml/(100g.min)、(8.11±1.44)s,两者比较差异均有统计学意义(P<0.05)。治疗组肿瘤区的BF、BV、PS、MTT值在治疗后第2周后从187.57ml/(100g.min)、5.21ml/100g、30.74ml/(100g.min)、3.87s改变为118.48ml/(100g.min)、4.21ml/100g、24.02ml/(100g.min)、4.27s,对照组从129.74ml/(100g.min)、3.22ml/100g、25.85ml/(100g.min)、3.68s改变为362.33ml/(100g.min)、10.86ml/100g、39.31ml/(100g.min)、3.54s,改善明显。结论 CT灌注成像技术能从血流动力学方面提供肿瘤定量信息,并能定量监测肿瘤微血管系对抗血管生成药物治疗的反应。

Objective To investigate the value of CT perfusion imaging in quantitative monitoring on microcirculation hemodynamics,differences between tumor and normal tissues,differences between mass center and edge,and on tumour microvascular responses to anti-angiogenesis therapy. Methods Fifteen male New Zealand white rabbits were established to VX2 tumor-bearing model. The animals were divided into 2 groups,anti-angiogenesis therapy （n=11,TNP-470,20 to 30 mg/kg）,and control （n=4）. DEC-CT scanning （80 kV,120 mA,20 cm VOF） was performed at 1 week after tumor implantation,1 week after anti-angiogenesis therapy,and 2 week after anti-angiogenesis therapy. Perfusion parameters,including blood flow （BF）,blood volume （BV）,mean transit time （MTT）,and permeability surface （PS） were calculated for tumor mass,tumor edge,tumor center and normal tissue. Results Significant differences of the average values were observed in BF,PS and MTT between tumor and normal tissue [149.32±30.99 vs 32.18±4.10 ml/（100 g·min）,28.24±5.15 vs 11.88±0.71 ml/（100 g·min）,2.79±0.66 vs 6.57±0.90 s,P0.05]. Difference was also seen between tumor edge [175.70±34.43 ml/（100 g·min）,32.43±6.52 ml/（100 g·min）,3.87±0.84 s] and tumor center [19.07±3.58 ml/（100 g·min）,18.75±2.10 ml/（100 g·min）,8.11±1.44 s]. The significant changes of BF,BV,PS,MTT were observed in the therapy group from 187.57 ml/（100 g·min）,5.21 ml/100 g,and 30.74 ml/（100 g·min）,3.87s respectively to 118.48 ml/（100 g·min）,4.21 ml/100 g,24.02 ml/（100 g·min）,and 4.27s in 2 weeks after anti-angiogenesis therapy,but not observed in control group [129.74 ml/（100 g·min）,3.22 ml/100 g,25.85 ml/（100 g·min）,and 3.68 s vs 362.33 ml/（100 g·min）,10.86 ml/100 g,39.31 ml/（100 g·min）,and 3.54 s]. Conclusion CT perfusion imaging can provide quantitative information on the changes in microcirculation hemodynamics for tumor,and it is a valuable tool for quantitative monitoring on tumour microvascular responses to anti-angiogenesis therapy.